1. Field of the Invention
Preferential complexation of one organic compound in a mixture of related compounds is a known technique for resolving mixtures of compounds having close boiling points. Of particular interest herein is a method for isolating 5-isopropyl-m-cresol by preferential complexation of this compound from a mixture of close-boiling isomers and di-isopropylated m-cresols.
2. State of the Art
Mixtures of isopropylated m-cresols are available as end-products or by-products from the acid-catalyzed isopropylation of m-cresol to make mixed isopropylated m-cresols. Such reactions produce many closely-boiling isopropylated m-cresols such as 6-isopropyl-m-cresol, commonly known as thymol, a pharmaceutical; 5-isopropyl-m-cresol, also known as 5-thymol or sym-thymol or m-thymol, a pesticide intermediate; and 4-isopropyl-m-cresol, also known as p-thymol; and 2-isopropyl-m-cresol, also known as 2-thymol. In the isopropylation of m-cresol to make one or more desirable isomers, a mixture of isomeric mono- and di-isopropylated m-cresols is usually produced. The isolation and purification of individual isopropylated m-cresols are very difficult by the use of conventional separation methods such as fractional distillation.
There are chemical processes known for separating closely-boiling organic compounds by methods other than or in addition to, energy-intensive physical separation techniques such as fractional distillation or fractional crystallization. These chemical processes involve a step of preferential complexation of one component of a mixture of closely-boiling compounds over other components of the mixture. For example, U.S. Pat. No. 4,267,389 to Leston, describes treating a phenolic mixture comprising para-cresol, methylated phenols and ethylated phenols, with an inorganic metal halide salt, such as calcium bromide, to remove para-cresol from the mixture. Removal of para-cresol from the mixture involves formation of a complex between para-cresol and calcium bromide, which complex forms preferentially over complexes between calcium bromide and other components of the phenolic mixture.
Mixtures of various alcohols may be resolved by treatment with a metal halide salt. For example, in Sharpless et al., J. Org. Chem., Vol. 40, No. 9, pp. 1252-1257 (1975) there is reported a study of competition between pairs of mono-hydroxy alcohols and mono-hydroxy phenols for complex formation with a metal halide salt. This study finds that phenols as a class form poorer complexes than alcohols of comparable melting points, probably because the phenols are weaker bases than the comparable alcohols.
There remains need, therefore, for methods for the isolation of 5-isopropyl-m-cresol from a mixture of closely-boiling isopropylated m-cresols by chemical complexation methods, rather than by fractional crystallization or distillation.